title: Systemic administration of FC-77 dampens ischemia-reperfusion-induced acute lung injury in rats.
abstract: Systemic administration of perfluorocarbons (PFCs) reportedly attenuates acute lung injury induced by acid aspiration and phorbol myristate acetate. However, the effects of PFCs on ischemia-reperfusion (IR)-induced lung injury have not been investigated. Typical acute lung injury was induced in rats by 60 min of ischemia and 60 min of reperfusion in isolated and perfused rat lung model. Rat lungs were randomly assigned to receive PBS (control), 1 % FC-77, IR only, or IR with different doses of FC-77 (0.1 %, 0.5 %, or 1 %). Subsequently, bronchoalveolar lavage fluid (BALF), perfusate, and lung tissues were collected to evaluate the degree of lung injury. IR caused a significant increase in the following parameters: pulmonary arterial pressure, capillary filtration coefficient, lung weight gain, lung weight/body weight ratio, wet/dry lung weight ratio, and protein concentration in BALF. TNF-α and cytokine-induced neutrophil chemoattractant-1 concentrations in perfusate samples and MDA concentration and MPO activities in lung tissues were also significantly increased. Histopathology showed increased septal thickness and neutrophil infiltration in the lung tissues. Furthermore, NF-κB activity was significantly increased in the lungs. However, pretreatment with 1 % FC-77 prior to IR significantly attenuated the increases in these parameters. In conclusion, our results suggest that systemic FC-77 administration had a protective effect on IR-induced acute lung injury. These protective mechanisms may have been mediated by the inhibition of NF-κB activation and attenuation of subsequent inflammatory response.
authors.affiliation: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shi-Jye
authors.initials: SJ
authors.lastname: Chu
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Wu
authors.forename: Fu-Chang
authors.initials: FC
authors.lastname: Ko
authors.forename: Geng-Chin
authors.initials: GC
authors.lastname: Wu
authors.forename: Rui-Ying
authors.initials: RY
authors.lastname: Li
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D005466:Fluorocarbons / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D005466:Fluorocarbons; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C429307:fluorocarbon 77